Wedelolactone suppresses cell proliferation and migration through AKT and AMPK signaling in melanoma

Purpose: Melanoma is a malignant tumor with high degree of malignancy, metastasis and high mortality. As melanoma is not sensitive to treatments, searching for new therapeutic agent is the priority. Wedelolactone (WDL) is a natural compound which has antiproliferation activities. In the current study, the effects of WDL on melanoma are evaluated and the underlying mechanisms are explored. Materials and methods: We treated melanoma cell line MV3 cells with WDL and monitored the cell proliferation, invasion and migration, the mRNA and protein levels of Bax and Bcl-2, expression of cell-cycle regulators including cyclin D, proliferating cell nuclear antigen (PCNA) and p21. We detected the effect of WDL on AKT and AMPK signaling pathways activations. Finally, we evaluated the inhibitory effect of WDL in xenograft nude mice model in vivo. Results: WDL inhibited MV3 cell proliferation, migration and invasion. WDL induced pro-apoptotic protein Bax expression but inhibited antiapoptotic protein Bcl-2 expression. WDL inhibited cyclin D expression while increased p21 expression. WDL inhibited AKT activation but induced AMPK activation. The induction of p21expression by WDL depended on AMPK signaling pathway. WDL inhibited melanoma in xenograft nude mice. Conclusion: WDL suppressed cell proliferation and regulated MV3 cell-cycle proteins through AKT and AMPK signaling in melanoma.